Pulmonary Gas Exchange

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1 Pulmonary Gas Exchange

2 ii Colloquium Digital Library of Life Sciences This e-book is an original work commissioned for the Colloquium Digital Library of Life Sciences: a curated collection of time-saving pedagogical resources for researchers and students who want to quickly get up to speed in a new area of life science/biomedical research. Each e-book available in Colloquium is an in-depth overview of a fast-moving or fundamental area of research, authored by a prominent researcher in the field. We call these resources Lectures because authors are asked to provide an authoritative, state-of-the-art overview of their area of expertise, in a manner that is accessible to a broad, diverse audience of scientists (similar to a plenary or keynote lecture at a symposium/meeting/colloquium). Readers are invited to keep current with advances in various disciplines, gain insight into fields other than their own, and refresh their understanding of core concepts in cell & molecular biology. For the full list of available Lectures, please visit; All Lectures available online as a PDF. Free Access for readers at institutions that license Colloquium. Please info@morganclaypool.com for more information.

3 iii Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease Editors D. Neil Granger, Louisiana State University Health Sciences Center Joey P. Granger, University of Mississippi Medical Center Physiology is a scientific discipline devoted to understanding the functions of the body. It addresses function at multiple levels, including molecular, cellular, organ, and system. An appreciation of the processes that occur at each level is necessary to understand function in health and the dysfunction associated with disease. Homeostasis and integration are fundamental principles of physiology that account for the relative constancy of organ processes and bodily function even in the face of substantial environmental changes. This constancy results from integrative, cooperative interactions of chemical and electrical signaling processes within and between cells, organs and systems. This ebook series on the broad field of physiology covers the major organ systems from an integrative perspective that addresses the molecular and cellular processes that contribute to homeostasis. Material on pathophysiology is also included throughout the ebooks. The state-of the-art treatises were produced by leading experts in the field of physiology. Each ebook includes stand-alone information and is intended to be of value to students, scientists, and clinicians in the biomedical sciences. Since physiological concepts are an ever-changing work-in-progress, each contributor will have the opportunity to make periodic updates of the covered material. Published titles (for future titles please see the website,

4 Copyright 2013 by Morgan & Claypool Life Sciences All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means electronic, mechanical, photocopy, recording, or any other except for brief quotations in printed reviews, without the prior permission of the publisher. Pulmonary Gas Exchange G. Kim Prisk and Susan R. Hopkins ISBN: paperback ISBN: ebook DOI: /C00087ED1V01Y201308ISP041 A Publication in the COLLOQUIUM SERIES ON INTEGRATED SYSTEMS PHYSIOLOGY: FROM MOLECULE TO FUNCTION TO DISEASE Lecture #41 Series Editors: D. Neil Granger, LSU Health Sciences Center, and Joey P. Granger, University of Mississippi Medical Center Series ISSN ISSN X ISSN print electronic

5 Pulmonary Gas Exchange G. Kim Prisk and Susan R. Hopkins University of California, San Diego COLLOQUIUM SERIES ON INTEGRATED SYSTEMS PHYSIOLOGY: FROM MOLECULE TO FUNCTION TO DISEASE #41

6 vi Abstract The lung receives the entire cardiac output from the right heart and must load oxygen onto and unload carbon dioxide from perfusing blood in the correct amounts to meet the metabolic needs of the body. It does so through the process of passive diffusion. Effective diffusion is accomplished by intricate parallel structures of airways and blood vessels designed to bring ventilation and perfusion together in an appropriate ratio in the same place and at the same time. Gas exchange is determined by the ventilation-perfusion ratio in each of the gas exchange units of the lung. In the normal lung ventilation and perfusion are well matched, and the ventilation-perfusion ratio is remarkably uniform among lung units, such that the partial pressure of oxygen in the blood leaving the pulmonary capillaries is less than 10 Torr lower than that in the alveolar space. In disease, the disruption to ventilation-perfusion matching and to diffusional transport may result in inefficient gas exchange and arterial hypoxemia. This volume covers the basics of pulmonary gas exchange, providing a central understanding of the processes involved, the interactions between the components upon which gas exchange depends, and basic equations of the process. Key words pulmonary, gas exchange, oxygen, carbon dioxide, ventilation, perfusion, lung, diffusion, airways, capillaries

7 vii Contents 1. Introduction Anatomy of the Gas Exchanger The Airway Tree The Pulmonary Circulation The Gas Exchange Barrier Gas Carriage Gas Carriage in Air Gas Carriage in Blood Inert Gas Transport O 2 Transport CO Transport CO 2 Transport Acid Base Balance Gas Exchange by Diffusion Diffusion vs. Perfusion Limitation Gas Exchange and the Matching of Ventilation and Perfusion Gas Exchange in an Ideal Lung Ventilation Alveolar Pco Alveolar Po Mixed Venous Blood The Effect of Ventilation-Perfusion Ratio on Gas Exchange Causes of Arterial Hypoxemia Low Inspired Oxygen Partial Pressure Hypoventilation Shunt... 44

8 viii Pulmonary Gas Exchange Diffusion Limitation Mismatch of Ventilation and Perfusion Non-uniformity of Ventilation Non-uniformity of Perfusion Non-uniformity of Ventilation-Perfusion Ratio The Consequence of Ventilation-Perfusion Mismatch on Pulmonary Gas Exchange Evaluating Pulmonary Gas Exchange Oxygen Uptake and Carbon Dioxide Production Diffusing Capacity Components of the Diffusing Capacity Ventilation-Perfusion Mismatch The A-a Gradient Shunt The Multiple Inert Gas Elimination Technique MIGET Single Breath Measurement of Ventilation-Perfusion Mismatch Imaging Summary References Author Biographies... 77

9 1 c h a p t e r 1 Introduction In much the same way that Christmas ornaments are best appreciated when hung on a Christmas tree, a discussion of the critical elements of mammalian pulmonary gas exchange (the ornaments) is perhaps best approached by having a framework on which to hang them (the tree). In that spirit, we will outline the requirements of the lung in the form of a list of specifications that the lung must meet. In each of the subsequent chapters, we will then address how the lung goes about meeting those specifications. In the chapters that follow this introduction, we have laid out how the human lung meets and deals with these specific requirements. When taken together, understanding how these design requirements have been met will provide a comprehensive view of the basics of pulmonary gas exchange in humans, and will serve as an introduction to how gas exchange can be evaluated in humans. As an aside, it is worth remembering that the design of human (and other mammalian) lungs is not the only way in which the requirements outlined above can be met. Of particular note, the pulmonary gas exchange system in birds uses a completely different design, one that some suggest may in fact be a more efficient design that that used in mammals [1]. This volume is devoted to human pulmonary gas exchange. In order to cover this, we spend Chapters 2 4 laying the groundwork for understanding gas exchange by considering the basic anatomy, how gases are carried in air, and in blood, and then how gas exchange occurs within the lung itself (by passive diffusion). Think of these as pieces of a jigsaw puzzle. Once all three have been read, the overall picture of gas exchange can be brought together. We do this in Chapter 5 (Matching Ventilation and Perfusion), which describes how gas and blood are brought together and how disruptions in this critical process are the principal cause of impaired gas exchange. Chapter 6 is a brief introduction of how gas exchange is measured and described. Wherever possible, we have tried to include references that will permit the reader to delve deeper into the subject matter that we have provided in this volume.

10 2 Pulmonary Gas Exchange Top Level requirement Table 1.1: Lung design requirements Provide O 2 necessary to meet metabolic needs of the entire body under all conditions of life. Remove CO 2 under same conditions. Specific requirements Location and space Space is provided in the upper (cranial) end of the torso adjacent to the heart. Under relaxed conditions ~4 liters of free space may be used. This space may be expanded to ~twice that of the relaxed state on a transient, as-required basis. O 2 and CO 2 transport Air shall be used as the source of O 2 and as the sink for produced CO 2. Blood shall be used to move O 2 to the tissues undergoing metabolism and to remove CO 2 from those tissues. Gas exchange mechanism The design shall be one of minimum energy usage. Air and blood distributions Given the requirements on gas transport and gas exchange (above) it is suggested that similar designs be utilized in the means by which air and blood are distributed. Gas exchange under conditions other than rest or normal environmental conditions The gas exchange system shall be capable of supporting conditions other than a resting state to include (but not limited to): High metabolic demand states High or low oxygen partial pressures

11 3 c h a p t e r 2 Anatomy of the Gas Exchanger The key factors in the design of the human lung stem directly from the constraints imposed by the volume of space available for the lung to occupy, by gas transport, and by the gas exchange mechanism itself. Of those elements, the principal factor that determines the anatomy of the mammalian lung stems from the fact that gas exchange occurs through the process of passive diffusion. Passive diffusion, whereby gas transport occurs down a gradient of partial pressure, requires no external energy source (in contrast to, for example, active ion transport occurring in the kidney), but requires a large surface area, and a very thin transport barrier in order to work efficiently. It is the combination of these requirements (large diffusive surface area, thin diffusive membrane), which must be satisfied simultaneously, that drives the anatomy of the lung. Note that Chapter 4 contains a detailed description of diffusive gas transport. The result these requirements is a gas exchange organ (the lung) with a gas exchanging surface area of ~ m 2 and a diffusive membrane the blood gas barrier with a thickness of ~0.3 µm [2 4]. Behind this gas exchange membrane is a sheet of blood so thin that it is only a single red blood cell in thickness. In addition, this entire sheet of blood is exchanged for another fresh sheet of blood every ¾ of a second on average. To attempt to visualize this, imagine taking a single glass of red wine, spreading it over an area the size of a tennis court, and then replacing the wine with another glass of wine in less than a second a remarkable feat! 2.1 THE AIRWAY TREE The challenge of fitting m 2 of membrane into a thoracic volume (at rest) of approximately 2 3 l is met by dividing up that volume into millions of tiny air sacs (alveoli). Original estimates of the number of alveoli in the human were ~300 million [3], but subsequent work has raised that number to an average of ~480 million [2]. Each alveolus is on average ~200 µm in diameter so that ~170 can be found in a single cubic millimeter of lung. Overall, this provides a lung with a total surface are of ~60 m 2. In order to connect each alveolus to the outside world for gas exchange, a branching network of airways forms the basic structure of the lung (Figure 2.1). In humans, this tree is in the form of

12 Pulmonary Gas Exchange Figure 2.1: A: Silicone rubber casts of the airways (in white) [5]. B: Casts in a region approximately the size of the red box in (A) that include airways (white), pulmonary arteries (red) and pulmonary veins (blue). Note the similarity of the branching structures. The pulmonary arteries accompany the airways, while the pulmonary veins are located between airway branches. Used with permission from Am J Respir Crit Care Med 2013; 187: a fairly regular branching dichotomy, where each airway splits into two somewhat equal daughter branches, at relatively similar branching angles. In this sense, the airway tree resembles many branching deciduous trees (e.g., an oak tree) where the trunk of the tree is analogous to the trachea. As an aside, it is worth noting that the regular dichotomy of the human lung is not the norm in most other mammalian lungs (such as the sheep and the pig), which tend to have a more dominant main airway from which small branches depart, more closely resembling a pine tree. Those are often referred to as monopodal branching patterns. This regular dichotomous branching pattern in humans led to a simplified description of the airway tree by Weibel in 1963 [4] in which the trachea was considered as generation zero, and with each succeeding bifurcation the number of airways doubled (Figure 2.2). In this model there are 23 generations after the trachea with alveoli appearing in the model at generation 17. This provides a useful splitting of the model into the conducting zone, generations 0 16 which play no part in gas exchange, but rather just serve as conduits to conduct air, and generations 17 23, the respiratory

13 Anatomy of the Gas Exchanger 5 Figure 2.2: A highly simplified but useful model describing the structure of the human airway tree. Each generation divides into two daughter branches that are smaller in size. This regular dichotomy continues for ~23 generations. The zone down to generation 16 contains no gas exchange units (alveoli) and is termed the conducting zone. Alveolarization begins at approximately generation 17. The model, termed Weibel-A, was originally published in 1963 [4]. Used with permission from West JB, Respiratory Physiology The Essentials; zone, where all gas exchange occurs. Despite the simplifying assumptions built into this model, it remains a useful means to describe the human airway tree. In this context, it is worth noting that the cast of an airway tree shown in Figure 2.1, in which the alveoli have been pruned away, is representative of generations 0 to ~16 and so shows only the conducting part of the lung. This is used to transport gas to the alveoli; no gas exchange occurs in the regions of the lung shown in the cast. This is important in terms of pulmonary gas exchange because airflow in the lung is reciprocal in nature; gas is both inspired and expired along the same pathway. As a consequence, the last amount of fresh gas taken in during inspiration fills the conducting airways, and remains there until expired, never reaching the alveoli where gas exchange

Section Two Diffusion of gases

Section Two Diffusion of gases Lecture 5: Partial pressure and the composition of gasses in air. Factors affecting diffusion of gases. Ventilation perfusion ratio effect on alveolar gas concentration.